Bevacizumab biosimilar(Shanghai Institute of Biological Products)

SIBP04 is a biosimilar of bevacizumab (Avastin®, Roche, Basel, Switzerland). This study evaluated the equivalence of SIBP04 to Avastin® as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer (nsqNSCLC).

In this randomized, double-blind, multi-center, phase 3 trial, we recruited patients with locally advanced or metastatic nsqNSCLC from 58 hospitals at China. Patients were randomly allocated 1:1 to receive SIBP04 or Avastin® (15 mg/kg) combined with paclitaxel (175 mg/m²) and carboplatin (area under curve [AUC] = 5.0, no more than 800 mg) (PC) regimens intravenously (3-week cycles, up to six cycles) followed by SIBP04 maintenance therapy. The primary endpoint was objective response rate (ORR), defined as the best overall response from the first dose to the 18th week, assessed by the independent review committee (IRC) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Clinical equivalence of the primary endpoint was done by comparing the two-sided 90% confidence interval (CI) of the ORR ratio (SIBP04 plus PC vs. Avastin® plus PC) in the per-protocol set (PPS) populaiton with the prespecified equivalence margin of 0.75-1.33. Secondary endpoints included progression-free survival, overall survival, duration of response, disease control rate, safety, immunogenicity, and pharmacological bioequivalence of steady-state trough concentrations.

From April 17, 2020, to April 20, 2021, 517 patients were randomly assigned to receive SIBP04 plus PC (n = 259) or Avastin® plus PC (n = 258). The ORR of the SIBP04 plus PC group was 55.6% (95% CI, 49.3-61.8) and that of the Avastin® plus PC group was 59.3% (95% CI, 53.0-65.4) in the full analysis set (FAS) population (P = 0. 3944). The ORR of the SIBP04 plus PC group was 62.6% (95% CI, 55.8-69.0) and that of the Avastin® plus PC group was 64.7% (95% CI, 58.0-71.0) in the PPS population (P = 0.6448). The ORR ratio (SIBP04 plus PC vs. Avastin® plus PC) was 0.94 (90% CI, 0.8270-1.0621) in the FAS population and 0.97 (90% CI, 0.8578-1.0900) in the PPS population, respectively, both within the prespecified equivalence margin of 0.75-1.33. Other efficacy endpoints, safety, immunogenicity, and pharmacokinetics were all comparable across the groups.

SIBP04 showed equivalent efficacy and safety profile to Avastin® in patients with locally advanced or metastatic nsqNSCLC. SIBP04 plus PC regimen will offer an alternative first-line treatment option for this patient population.

Clinicaltrials.gov, identifier NCT05318443.